What medications can cause numbness and tingling?

Medications That Cause Numbness and Tingling

Chemotherapy agents, particularly taxanes (paclitaxel) and platinum compounds (oxaliplatin, cisplatin), are the most common medications causing numbness and tingling, affecting 30-40% of patients, followed by fluoroquinolone antibiotics (ciprofloxacin, levofloxacin) which carry significant risk of peripheral neuropathy including severe forms like Guillain-Barré syndrome. 1, 2

Chemotherapy-Induced Peripheral Neuropathy (CIPN)

High-Risk Chemotherapy Agents

Taxanes and platinum compounds are the primary culprits:

• Paclitaxel causes predominantly sensory neuropathy with numbness and tingling more prominent in lower extremities during treatment, typically improving over several months after completion 1
• Oxaliplatin produces acute cold-induced symptoms and chronic neuropathy that paradoxically worsens for 2-3 months after stopping treatment (coasting phenomenon), with upper extremity symptoms initially more severe than lower 1
• Vinca alkaloids affect small nerve fibers and can cause autonomic involvement with abdominal pain, constipation, and postural hypotension 1
• Bortezomib causes small fiber neuropathy with burning sensations in hands and feet 1
• Thalidomide produces sensory neuronopathy affecting dorsal root ganglia, often irreversible 1

Clinical Presentation Pattern

The typical presentation follows a predictable pattern:

• Symptoms begin as numbness and tingling in fingers and toes in a symmetric "stocking-glove" distribution 1
• Sensory symptoms appear earlier and are more prominent than pain 1
• Progression occurs proximally as severity worsens 1
• Motor and autonomic involvement is less common but can occur 1

Fluoroquinolone Antibiotics

Ciprofloxacin and levofloxacin carry FDA warnings for peripheral neuropathy risk:

• Significant disproportionality signals detected: ciprofloxacin (EBGM 3.24) and levofloxacin (EBGM 3.36) 2
• Can cause acute bilateral numbness and tingling in upper and lower extremities after as few as 2 doses 3
• Risk includes severe forms like Guillain-Barré syndrome (EBGM 4.15 for ciprofloxacin) 2
• Symptoms can be permanent and disabling, affecting multiple body systems 3, 4
• Alternative antibiotics should be used unless fluoroquinolone benefit clearly outweighs neuropathy risk 2

Aromatase Inhibitors

Up to 50% of postmenopausal women on aromatase inhibitors report:

• Joint pain (arthralgias) and muscle pain (myalgias) 1
• Severe enough in 20% to cause treatment discontinuation 1
• Numbness reported in 29-81% of breast cancer patients on systemic therapy 1

Targeted Cancer Therapies

Ibrutinib (Bruton's tyrosine kinase inhibitor):

• Can cause progressive polyneuropathy with numbness and tingling in legs 5
• Typically develops after prolonged use (reported at 10 months) 5
• May improve with dose reduction or temporary discontinuation 5

Other Medication Classes

Additional drugs implicated in peripheral neuropathy include:

• Vinca alkaloids: Dose-limiting neuropathy is universal 6
• Multiple other drug classes can rarely cause neuropathy through dose-dependent axonal degeneration 6

Risk Factors Requiring Caution

Pre-existing conditions increase vulnerability to drug-induced neuropathy:

• Diabetes mellitus 1, 6
• Hereditary peripheral neuropathy (family or personal history) 1
• Hepatic or renal failure 6
• Malnutrition 6
• Congenital cervical stenosis (for bilateral hand symptoms) 7

Management Approach

Prevention Strategy

• Screen for pre-existing neuropathy before starting neurotoxic medications 1
• Restrict use in high-risk patients when alternatives exist 6
• Consider prophylactic vitamin supplementation in some cases 6

Treatment of Established Neuropathy

Duloxetine is the only evidence-based pharmacologic treatment for painful peripheral neuropathy with numbness and tingling:

• Recommended as first-line therapy 1, 7
• Must be tapered slowly when discontinuing to avoid withdrawal symptoms 1

Non-pharmacologic interventions with supportive evidence:

• Physical activity and exercise therapy 1, 7
• Acupuncture for pain management 1, 7
• Acetaminophen and NSAIDs for associated pain 1, 7

Not recommended based on current evidence:

• Gabapentin/pregabalin 1
• Tricyclic antidepressants 1
• Topical amitriptyline/ketamine preparations 1
• Acetyl-L-carnitine (may worsen symptoms) 1

Critical Decision Points

Discontinue or reduce the offending medication when:

• Neuropathy symptoms develop or worsen 6, 5
• Severity threatens quality of life or function 1
• Alternative treatments are available 2

For chemotherapy patients, balance cancer treatment efficacy against neuropathy severity, as CIPN can limit chemotherapy dosing and negatively impact cancer outcomes 1